A Mitochondrial tRNA Mutation Causes Axonal CMT in a Large Venezuelan Family.

OBJECTIVE: The objective of this study was to identify the genetic cause for progressive peripheral nerve disease in a Venezuelan family. Despite the growing list of genes associated with Charcot-Marie-Tooth disease, many patients with axonal forms lack a genetic diagnosis. METHODS: A pedigree was constructed, based on family clinical data. Next-generation sequencing of mitochondrial DNA (mtDNA) was performed for 6 affected family members. Muscle biopsies from 4 family members were used for analysis of muscle histology and ultrastructure, mtDNA sequencing, and RNA quantification. Ultrastructural studies were performed on sensory nerve biopsies from 2 affected family members. RESULTS: Electrodiagnostic testing showed a motor and sensory axonal polyneuropathy. Pedigree analysis revealed inheritance only through the maternal line, consistent with mitochondrial transmission. Sequencing of mtDNA identified a mutation in the mitochondrial tRNAVal (mt-tRNAVal ) gene, m.1661A>G, present at nearly 100% heteroplasmy, which disrupts a Watson-Crick base pair in the T-stem-loop. Muscle biopsies showed chronic denervation/reinnervation changes, whereas biochemical analysis of electron transport chain (ETC) enzyme activities showed reduction in multiple ETC complexes. Northern blots from skeletal muscle total RNA showed severe reduction in abundance of mt-tRNAVal , and mildly increased mt-tRNAPhe , in subjects compared with unrelated age- and sex-matched controls. Nerve biopsies from 2 affected family members demonstrated ultrastructural mitochondrial abnormalities (hyperplasia, hypertrophy, and crystalline arrays) consistent with a mitochondrial neuropathy. CONCLUSION: We identify a previously unreported cause of Charcot-Marie-Tooth (CMT) disease, a mutation in the mt-tRNAVal , in a Venezuelan family. This work expands the list of CMT-associated genes from protein-coding genes to a mitochondrial tRNA gene. ANN NEUROL 2020;88:830-842.

[Systematic of the fish Petenia splendida (Perciformes: Cichlidae) of Lake Petén Itzá, Guatemala]. / Sistemática del pez Petenia splendida (Perciformes: Cichlidae) en el lago Petén Itzá, Guatemala.

The Lake Petén Itzá is located in the multiple use zone of the Maya Biosphere Reserve. It belongs to the subtropical moist forest (warm) life zone, and has very important flora and fauna diversities. Among the fish species, the white fish (Petenia splendida) is of high commercial value. The main goal of the present work was to clarify the taxonomic position of the two forms of the white fish in Petén (Guatemala), and to compare it with the Usumacinta (Mexico) form, based on the collected material from 1978 and 2006 (Usumacinta), and collections made during 2008 and 2009 in the Lake Petén Itzá. Samples were obtained from 10 different locations in the lake. From the total of 57 fish specimens collected, 50 fish were selected (25 yellow form and 25 silver form); besides, 21 specimens from 10 locations of the Usumacinta river in Mexico, from the Fish Collection, FCB, UANL. A total of 36 morphometric and 16 meristic characteristics, were analyzed, and also coloration, habitat and fishing method. This study reports the P. splendida of the Lake Petén Itzá with the following characteristics: the yellow form at a depth of 0.5-1.5m with dorsal fin XIV-(XV)-XVI/11-(12)-13, the silver form at a depth of 2-3m with dorsal fin XIV-(XV)-XVI/10-(12)-13, and the Usumacinta form with a dorsal fin XIV-(XV)-XV/12-(13)-13. The discrimination analysis demonstrates a differentiation among the three analyzed populations. Some of the characteristics are the ocular diameter, the anal source-pelvic source distance and the dorsal source-anal source distance. The geographic area studied has a high diversity of fish fauna along the watershed, and it is possible to observe the anthropogenic damage, due to the overexploitation based the unapplicability of the existent regulation and the urbanization. If this situation continues it could jeopardize the survival of this emblematic specie.

Sistemática del pez Petenia splendida (Perciformes: Cichlidae) en el lago Petén Itzá, Guatemala

Systematic of the fish Petenia splendida (Perciformes: Cichlidae) of Lake Petén Itzá, Guatemala. The Lake Petén Itzá is located in the multiple use zone of the Maya Biosphere Reserve. It belongs to the subtropical moist forest (warm) life zone, and has very important flora and fauna diversities. Among the fish species, the white fish (Petenia splendida) is of high commercial value. The main goal of the present work was to clarify the taxonomic position of the two forms of the white fish in Petén (Guatemala), and to compare it with the Usumacinta (Mexico) form, based on the collected material from 1978 and 2006 (Usumacinta), and collections made during 2008 and 2009 in the Lake Petén Itzá. Samples were obtained from 10 different locations in the lake. From the total of 57 fish specimens collected, 50 fish were selected (25 yellow form and 25 silver form); besides, 21 specimens from 10 locations of the Usumacinta river in Mexico, from the Fish Collection, FCB, UANL. A total of 36 morphometric and 16 meristic characteristics, were analyzed, and also coloration, habitat and fishing method. This study reports the P. splendida of the Lake Petén Itzá with the following characteristics: the yellow form at a depth of 0.5-1.5m with dorsal fin XIV-(Xv)-XVI/11-(12)-13, the silver form at a depth of 2-3m with dorsal fin XIV-(XV)-XVI/10-(12)-13, and the Usumacinta form with a dorsal fin XIV-(XV)-XV/12-(13)-13. The discrimination analysis demonstrates a differentiation among the three analyzed populations. Some of the characteristics are the ocular diameter, the anal source-pelvic source distance and the dorsal source-anal source distance. The geographic area studied has a high diversity of fish fauna along the watershed, and it is possible to observe the anthropogenic damage, due to the overexploitation based the unapplicability of the existent regulation and the urbanization. If this situation continues it could jeopardize the survival of this emblematic specie. Rev. Biol. Trop. 59 (3): 1205-1216. Epub 2011 September 01.

El Lago Petén Itzá se ubica en la zona de usos múltiples de la Reserva de la Biosfera Maya, entre sus especies ícticas encontramos al pez blanco (Petenia splendida) de alto valor comercial. El propósito del presente trabajo es aclarar la posición taxonómica de las dos formas de pez blanco de Petén y compararlas con la forma del Usumacinta. Entre 2008 y 2009 se recolectaron 25 ejemplares de la forma amarilla y 25 de la plateada en 10 localidades del lago Petén Itzá y 21 en la cuenca del Usumacinta durante 1978 y 2006; se revisaron 36 características morfométricas y 16 merísticas, así como coloración, hábitat y forma de pesca. La P. splendida del Lago presenta las siguientes características: la forma amarilla se encuentra a una profundidad entre 0.5 y 1.5m, tiene aleta dorsal XIV-(XV)-XVI/11-(12)-13; la plateada esta a profundidades entre 2-3m, presenta aleta dorsal XIV-(XV)-XVI/10-(12)-13, mientras que la forma del Usumacinta posee aleta dorsal XIV-(XV)-XV/12-(13)-13. El análisis discriminante muestra una diferenciación entre las tres poblaciones analizadas aunque no es determinante. La fauna de peces de la cuenca del área de estudio presenta alta diversidad, se observa daño antropogénico producto de la sobreexplotación, por la falta de aplicación de la reglamentación existente y la urbanización.

Hepcidin treatment in Hfe-/- mice diminishes plasma iron without affecting erythropoiesis.

BACKGROUND: Iron is essential for mammalian metabolism and its cellular concentration is controlled by regulating its acquisition and storage. Haemochromatosis is a condition involving iron overload that is characterised by increased duodenal iron absorption and a progressive accumulation of iron in vital organs. Hepcidin is the main hormone that regulates iron homoestasis and it is secreted by the liver. MATERIALS AND METHODS: We have studied how extended hepcidin administration affects the iron load status, plasma and tissue iron concentration, erythropoiesis and the expression of proteins involved on iron homeostasis in haemochromatotic (Hfe(-/-)) and wild-type mice. RESULTS: Hepcidin reverted the high plasma iron concentrations in Hfe(-/-) mice to normal values. The high concentration of hepatic iron was not altered in the liver of these Hfe(-/-) mice. Hepcidin administration did not disturb erythropoiesis in either Hfe(-/-) or wild-type mice and likewise, hepcidin did not modify the expression of any protein analysed in the liver, duodenum or spleen of Hfe(-/-) and wild-type mice. These data confirm that hepcidin administration diminishes plasma iron concentrations. CONCLUSION: Treatment with sustained doses of hepcidin diminishes plasma iron concentrations in Hfe(-/-) mice.